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The deployment of antiviral therapy typically requires the clinician to strike a delicate balance between targeting virally encoded functions required for production of progeny viruses and avoiding toxicity to the host cellular functions subverted by the viral replication machinery. Accordingly, as a part of the trade-off for eliciting antiviral effect, many antivirals historically have induced considerable toxicity in the host cell as well. A watershed moment in the history of antiviral drug discovery was the development of the drug acyclovir, one of a series of drugs that was developed that blocked nucleic acid synthesis only in virally infected cells without damaging the uninfected host cells (because a viral enzyme, thymidine kinase, is required to phosphorylate the compound to its active form). This discovery resulted in the awarding of a Nobel Prize to Dr. Gertrude Elion in 1988.

Today, a number of effective antivirals currently are licensed and available, and are important in the management of infections caused by herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), hepatitis B and C viruses, influenza A and B viruses, and human immunodeficiency virus (HIV). To maximize therapeutic effectiveness, treatment should generally be initiated as early as possible in the course of infection. Under some circumstances, antivirals may be effective in prophylaxis against acquisition or reactivation of infection. The advent and increased utilization of rapid-diagnosis molecular platforms for viral infections has enabled the more timely use of antiviral therapy in many clinical settings, so a working knowledge of available antivirals in pediatric practice is essential.

Although most early experience with antivirals in pediatric practice was accrued in the inpatient setting, structural and biochemical modifications of antiviral compounds have led to the development of many agents with excellent bioavailability after oral administration. Many of these drugs are now used extensively in the outpatient setting (Table 240-1). However, severe viral infections, especially in immunocompromised hosts, still require aggressive parenteral therapy, usually in the inpatient setting (Table 240-2).


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